DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Kim, Mi-Young | - |
dc.contributor.advisor | 김미영 | - |
dc.contributor.author | Lee, Ho-Yoen | - |
dc.date.accessioned | 2019-08-22T02:43:15Z | - |
dc.date.available | 2019-08-22T02:43:15Z | - |
dc.date.issued | 2019 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=842097&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/264761 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 생명과학과, 2019.2,[v, 80 :] | - |
dc.description.abstract | Brain metastasis in breast cancer is particularly deadly, but effective treatments remain out of reach due to insufficient information about the mechanisms underlying brain metastasis and the potential vulnerabilities of brain-metastatic breast cancer cells. Here, human breast cancer cells and their brain-metastatic derivatives (BrMs) were used to investigate synthetic lethal interactions in BrMs. First, it was demonstrated that c-MYC activity is increased in BrMs and is required for their brain-metastatic ability in a mouse xenograft model. Specifically, c-MYC enhanced brain metastasis by facilitating the following processes within the brain microenvironment: 1) invasive growth of BrMs, 2) macrophage infiltration, and 3) GAP-junction formation between BrMs and astrocytes by up-regulating connexin 43 (GJA1/Cx43). Furthermore, RNA-sequencing (RNA-seq) analysis uncovered a set of c-MYC-regulated genes whose expression is associated with higher risk for brain metastasis in breast cancer patients. Paradoxically, however, increased c-MYC activity in BrMs rendered them more susceptible to TRAIL (TNF-related apoptosis-inducing ligand)-induced apoptosis. In summary, these data not only reveal the brain metastasis-promoting role of c-MYC and a subsequent synthetic lethality with TRAIL, but also delineate the underlying mechanism. This suggests TRAIL-based approaches as potential therapeutic options for brain-metastatic breast cancer. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | c-MYC▼aBrain metastasis▼aBreast cancer▼aTRAIL▼aApoptosis | - |
dc.subject | c-MYC▼a뇌전이▼a유방암▼aTRAIL▼a세포자살 | - |
dc.title | Investigating the role of c-MYC for TRAIL-induced apoptosis and breast cancer metastasis to the brain | - |
dc.title.alternative | 유방암의 뇌 전이와 TRAIL 민감성 조절에 관한 c-MYC의 기능 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :생명과학과, | - |
dc.contributor.alternativeauthor | 이호연 | - |
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